Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet
Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet
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DOI：
10.1016/j.bbrc.2007.10.083
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发表时间：
2007-12-28
影响因子：
3.1
通讯作者：
Sakaida, Isao
中科院分区：
文献类型：
--
作者：
Jin, Haiyan;Yamamoto, Naoki;Sakaida, Isao
肾素-血管紧张素系统通过激活肝星状细胞参与肝纤维化。替米沙坦（Tel）是一种血管紧张素II型1受体拮抗剂，可作为选择性过氧化物酶体增殖体激活受体γ激活剂。我们研究了Tel对肝纤维化、体内肿瘤前病变和体外原代造血干细胞的影响。在体内研究中，我们使用了缺乏胆碱的l -氨基酸（CDAA）饮食诱导的大鼠NASH模型。用CDAA喂养大鼠8周，诱导肝纤维化和肿瘤前病变，再与Tel共给药10周。Tel通过下调TGF β 1和TIMP-1、2，提高MMP-13表达，抑制肝纤维化和瘤前病变。Tel抑制hsc的活化和增殖。这些结果表明，Tel可能是一种治疗NASH相关肝纤维化的有希望的药物。(C) 2007爱思唯尔公司版权所有。
Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor gamma activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGF beta 1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis. (C) 2007 Elsevier Inc. All rights reserved.